AB0442 EVEN IN SYSTEMIC LUPUS ERYTHEMATOSUS THAT HAS ACHIEVED SUSTAINED LLDAS, ADDITIONAL ADMINISTRATION OF HYDROXYCHLOROQUINE SHOULD BE CONSIDERED.
Authors: R. Wakiya, K. Ueeda, H. Shimada, S. Nakashima, M. Kato, T. Miyagi, K. Sugihara, M. Mizusaki, R. Mino, T. Kameda, H. Dobashi
Journal: Annals of the Rheumatic Diseases (2022)

Background Hydroxychloroquine (HCQ) therapy is recommended as a baseline treatment for all patients with systemic lupus erythematosus (SLE) due to its various benefits (1). However, it is not clear to what extent HCQ contributes to improvement in SLE patients with stable disease activity. It has also been reported that HCQ is effective in improving the prognosis of life caused by atherosclerotic lesions in SLE, but the mechanism of this effect has not been fully elucidated. Objectives The purpose of this study was to determine the benefit of additional HCQ administration in SLE with controlled disease activity, who achieved the sustained LLDAS. Methods The study included patients with SLE who started additional HCQ treatment between January 2016 and December 2019 at our institution, those who sustained LLDAS achievement for at least 3 months prior to starting HCQ treatment. These patients did not change their immunosuppressant and glucocorticoid regimens for more than three months after starting HCQ. The effect of HCQ was assessed at the beginning and 3 months after administration. The disease activity was measured by SELENA-SLEDAI, SLE-DAS, and immunoserological parameters including serum complement levels and anti-DNA antibodies. The factors that are known to associated with pathogenesis of atherosclerosis, such as serum TNF-α, IL-6, IL-8, MCP-1, adiponectin, leptin, resistin, S100A8, and S100A9, were measured by ELISA. Results Of the 110 SLE patients who received additional HCQ at our institution, 27 patients who had achieved LLDAS from at least 3 months prior to HCQ administration were included in this study. Patient characteristics are represented in Table 1. SLEDAI scores, SLE-DAS scores and serum anti-dsDNA antibodies were observed to be significantly reduced after HCQ treatment compared to baseline. After 3 months of HCQ treatment, serum lipid markers such as triglyceride (TG), low-density lipoprotein (LDL) cholesterol and atherosclerotic index, which are associated with the development of atherosclerosis, were significantly reduced compared to baseline (TG, LDL and atherosclerotic index: p&lt;0.05). Cytokines such as TNF-α, IL-6, MCP-1, S100A8, S100A9, leptin, and resistin were found to be significantly decreased, and serum adiponectin was significantly increased. (TNF-α, IL-6, MCP-1, leptin: p &lt; 0.05. S100A8, S100A9, adiponectin, resistin: p &lt; 0.0001, Figure 1). Table 1. Characteristics of patients with SLE enrolled in this study. Characteristics N = 27 Female, no. (%) 24 (88.9) Age, years, mean ± SD 44.4 ± 11.6 Disease duration, years, mean ± SD 18.3 ± 12.2 BMI, mean ± SD 21.9 ± 3.0 Concomitant immunosuppressive treatments Prednisone, no. (%) n = 23 Median dosage, mg/day # 5 (3.0–5.0) Triglyceride, mg/dL # 102 (73–149) High-density lipoprotein cholesterol, mg/dL # 59 (43–66.5) Low-density lipoprotein cholesterol, mg/dL # 108 (96–122) Arteriosclerotic index # 2 (1.7–2.5) Disease activity SLEDAI score # 4 (2–4) SLE-DAS score # 2.076 (1.12–3.50) Anti-dsDNA antibody, IU/ml # 5.2 (5–15.6) dsDNA positive, no. (%) 10 (37.0) C3, mg/dL # 76 (61–100) C4, mg/dL # 14 (10–22) CH50, U/mL # 34.1 (29.7–39.6) # Nonparametric distributions were represented as median (interquartile range). Anti-dsDNA positive means that anti-dsDNA titer increases to &gt;12 IU/mL. Figure 1. Serum cytokine levels before and after hydroxychloroquine treatment Serum levels of the indicated cytokines and factors were measured at baseline and after 3 months (3M) of treatment with HCQ. The gray lines show the values for individual patients, and the thick red line shows the average value. P-values were determined using the Wilcoxon signed-rank test. A p-value of less than 0.05 was considered statistically significant. Conclusion The addition of HCQ medication to SLE patients who achieve the clinical therapeutic goal of LLDAS without HCQ may prevent progression of atherosclerosis in addition to further reducing disease activity. References [1]Fanouriakis A, Kostopoulou M, Alunno A, et al. Ann Rheum Dis. 2019;78:736-745. Disclosure of Interests None declared